AOD9604
AOD9604, also called LAT8881, is Tyr-hGH177-191 with a disulfide bond. It reached multiple human obesity and pain trials. The large obesity program missed its weight-loss endpoints, and three later pain trials did not show a significant or consistent active-versus-placebo benefit.
modified C-terminal human growth-hormone fragment
- Sequence YLRIVQCRSVEGSCGF with a Cys7-Cys14 disulfide
- Different from unmodified HGH Fragment 176-191
- Large oral obesity program ended after efficacy failure
- No FDA-approved AOD9604 drug
Is AOD9604 the same as HGH Fragment 176-191?
No. AOD9604 is YLRIVQCRSVEGSCGF, a Tyr-hGH177-191 peptide with a disulfide between its two cysteines. Unmodified HGH Fragment 176-191 begins with phenylalanine. Free-base and acetate bulk substances also have distinct quality attributes.
FDA 2024 review · identity, trials, quality
FDA staff briefing document
US Food and Drug Administration, November 2024.
FDA defined free-base AOD9604 as a 16-amino-acid Tyr-hGH177-191 fragment with a Cys7-Cys14 disulfide, separated it from AOD9604 acetate, reviewed obesity and safety data, identified formulation and impurity gaps, and concluded the criteria weighed against 503A bulks-list inclusion.
- Study design
- Regulatory evidence and quality review
Does AOD9604 cause meaningful weight loss?
The large 24-week randomized obesity study missed its primary and secondary weight-loss endpoints, and the sponsor terminated the obesity program. Earlier subgroup findings were exploratory.
Has it worked for pain instead?
Not convincingly. Posted trials in neuropathic pain, migraine, and lumbar radicular pain did not show a persuasive active-versus-placebo pain benefit.
NCT03865953 · primary endpoint negative
Posted randomized trial results
ClinicalTrials.gov NCT03865953.
Fifty-three adults entered a randomized crossover trial of 30 mg oral LAT8881 twice daily. Mean pain changed by -0.87 with LAT8881 and -0.74 with placebo; the net difference was -0.14 points, 95% CI -0.76 to 0.49, P=0.67.
- Participants / model
- Adults with diabetic peripheral neuropathy or post-herpetic neuralgia
- Treatment
- Oral LAT8881 30 mg twice daily versus placebo
- Follow-up
- Four weeks per crossover period
- Study design
- Randomized, double-blind, placebo-controlled crossover trial
- Funding
- Lateral Pharma Pty Ltd
NCT04153409 · no significant pain timepoint
Posted randomized trial results
ClinicalTrials.gov NCT04153409.
Twenty-one adults entered a randomized crossover proof-of-concept trial. None of the seven posted active-versus-placebo pain comparisons from 30 minutes through 24 hours was statistically significant; the smallest P value was 0.1488 at two hours.
- Participants / model
- Adults treating an acute migraine attack
- Treatment
- Single 60 mg oral LAT8881 dose versus placebo
- Follow-up
- Pain measured through 24 hours
- Study design
- Randomized, placebo-controlled crossover proof-of-concept trial
- Funding
- Lateral Pharma Pty Ltd
NCT05298306 · small safety and pain study
Posted randomized trial results
ClinicalTrials.gov NCT05298306.
The two-part study enrolled 26 adults. Part A found no serious or grade 3-4 events after single IV doses. Part B compared 1.8 mg/kg with placebo in a 17-per-period crossover and posted no persuasive separation across the repeated six-hour pain measurements.
- Participants / model
- Adults with lumbar radicular pain
- Treatment
- Single IV LAT8881 doses from 0.8 to 1.8 mg/kg or placebo
- Follow-up
- Safety through 14 days; pain through six hours
- Study design
- Randomized, double-blind, placebo-controlled two-part study
- Funding
- Lateral Pharma Pty Ltd
ASX 2007 · weight-loss endpoints missed
Sponsor exchange disclosure
Metabolic Pharmaceuticals Ltd, Australian Securities Exchange announcement, 21 February 2007.
The sponsor disclosed that its 24-week randomized obesity trial enrolled 536 people and did not show a significant AOD9604 effect on the primary or secondary weight-loss endpoints. It terminated the obesity program. Subgroup signals were exploratory and did not rescue the overall result.
- Participants / model
- Adults with obesity in a diet-and-exercise program
- Treatment
- Oral AOD9604 at 0.25, 0.5, or 1 mg daily versus placebo
- Follow-up
- 24 weeks after a placebo run-in
- Study design
- Randomized, double-blind, placebo-controlled Phase 2B trial
- Funding
- Metabolic Pharmaceuticals Ltd
FDA 2024 review · identity, trials, quality
FDA staff briefing document
US Food and Drug Administration, November 2024.
FDA defined free-base AOD9604 as a 16-amino-acid Tyr-hGH177-191 fragment with a Cys7-Cys14 disulfide, separated it from AOD9604 acetate, reviewed obesity and safety data, identified formulation and impurity gaps, and concluded the criteria weighed against 503A bulks-list inclusion.
- Study design
- Regulatory evidence and quality review
What was the original hypothesis?
AOD9604 was designed to preserve a C-terminal growth-hormone fragment’s fat-metabolism activity without full-length growth hormone’s growth and IGF-1 effects. Human safety studies generally did not raise IGF-1, but the obesity efficacy test still failed.
Six-trial summary · sponsor-affiliated
Pooled clinical safety report
Stier H, Vos E, Kenley D. Journal of Endocrinology and Metabolism, 2013.
The paper summarizes six trials with 893 participants using single intravenous or oral exposure through 24 weeks. It reports no treatment-related serious event, no anti-AOD9604 antibodies in tested subsets, and no material IGF-1 or glucose signal. The authors included company personnel, the studies were heterogeneous, and subcutaneous use was not tested.
- Participants / model
- 893 participants across six sponsor trials, mainly adults with obesity
- Treatment
- Single IV doses or oral AOD9604 across multiple schedules
- Follow-up
- Single dose through 24 weeks
- Study design
- Sponsor-affiliated pooled safety narrative across six trials
- Funding
- Metabolic Pharmaceuticals program
The individual studies were not all independently peer-reviewed.
Read the original sourceFDA 2024 review · identity, trials, quality
FDA staff briefing document
US Food and Drug Administration, November 2024.
FDA defined free-base AOD9604 as a 16-amino-acid Tyr-hGH177-191 fragment with a Cys7-Cys14 disulfide, separated it from AOD9604 acetate, reviewed obesity and safety data, identified formulation and impurity gaps, and concluded the criteria weighed against 503A bulks-list inclusion.
- Study design
- Regulatory evidence and quality review
ASX 2007 · weight-loss endpoints missed
Sponsor exchange disclosure
Metabolic Pharmaceuticals Ltd, Australian Securities Exchange announcement, 21 February 2007.
The sponsor disclosed that its 24-week randomized obesity trial enrolled 536 people and did not show a significant AOD9604 effect on the primary or secondary weight-loss endpoints. It terminated the obesity program. Subgroup signals were exploratory and did not rescue the overall result.
- Participants / model
- Adults with obesity in a diet-and-exercise program
- Treatment
- Oral AOD9604 at 0.25, 0.5, or 1 mg daily versus placebo
- Follow-up
- 24 weeks after a placebo run-in
- Study design
- Randomized, double-blind, placebo-controlled Phase 2B trial
- Funding
- Metabolic Pharmaceuticals Ltd
What does the human safety record cover?
Sponsor trials exposed nearly 900 participants, mainly through oral dosing plus limited single intravenous exposure. They did not test chronic subcutaneous or transdermal use, and FDA identifies formulation and impurity gaps.
- Route: the longest studies were oral; common market injection is not equivalent.
- Study independence: the pooled safety paper includes sponsor personnel and summarizes trials with limited independent publication.
- Chemistry: disulfide reduction, dimerization, aggregation, salt form, sterility, and endotoxin control are product-specific.
Six-trial summary · sponsor-affiliated
Pooled clinical safety report
Stier H, Vos E, Kenley D. Journal of Endocrinology and Metabolism, 2013.
The paper summarizes six trials with 893 participants using single intravenous or oral exposure through 24 weeks. It reports no treatment-related serious event, no anti-AOD9604 antibodies in tested subsets, and no material IGF-1 or glucose signal. The authors included company personnel, the studies were heterogeneous, and subcutaneous use was not tested.
- Participants / model
- 893 participants across six sponsor trials, mainly adults with obesity
- Treatment
- Single IV doses or oral AOD9604 across multiple schedules
- Follow-up
- Single dose through 24 weeks
- Study design
- Sponsor-affiliated pooled safety narrative across six trials
- Funding
- Metabolic Pharmaceuticals program
The individual studies were not all independently peer-reviewed.
Read the original sourceNCT05298306 · small safety and pain study
Posted randomized trial results
ClinicalTrials.gov NCT05298306.
The two-part study enrolled 26 adults. Part A found no serious or grade 3-4 events after single IV doses. Part B compared 1.8 mg/kg with placebo in a 17-per-period crossover and posted no persuasive separation across the repeated six-hour pain measurements.
- Participants / model
- Adults with lumbar radicular pain
- Treatment
- Single IV LAT8881 doses from 0.8 to 1.8 mg/kg or placebo
- Follow-up
- Safety through 14 days; pain through six hours
- Study design
- Randomized, double-blind, placebo-controlled two-part study
- Funding
- Lateral Pharma Pty Ltd
FDA safety page · limited proposed-route evidence
FDA safety communication
US Food and Drug Administration.
FDA cites immunogenicity, peptide-impurity, and API-characterization concerns and notes serious adverse events of unclear causality. Evidence for proposed compounded routes is limited.
- Study design
- Agency safety summary
FDA 2024 review · identity, trials, quality
FDA staff briefing document
US Food and Drug Administration, November 2024.
FDA defined free-base AOD9604 as a 16-amino-acid Tyr-hGH177-191 fragment with a Cys7-Cys14 disulfide, separated it from AOD9604 acetate, reviewed obesity and safety data, identified formulation and impurity gaps, and concluded the criteria weighed against 503A bulks-list inclusion.
- Study design
- Regulatory evidence and quality review
Is AOD9604 FDA approved or FDA-GRAS?
FDA approval records contain no AOD9604 drug. The FDA GRAS Notice Inventory contains no AOD9604 notice or response letter. A private self-affirmed food-use conclusion would not approve injection or disease treatment. WADA prohibits GH fragments.
FDA 2024 review · identity, trials, quality
FDA staff briefing document
US Food and Drug Administration, November 2024.
FDA defined free-base AOD9604 as a 16-amino-acid Tyr-hGH177-191 fragment with a Cys7-Cys14 disulfide, separated it from AOD9604 acetate, reviewed obesity and safety data, identified formulation and impurity gaps, and concluded the criteria weighed against 503A bulks-list inclusion.
- Study design
- Regulatory evidence and quality review
FDA GRAS records · no AOD9604 notice
Regulatory database record set
US FDA GRAS Notice Inventory records.
The FDA GRAS Notice Inventory contained no entry or response letter for AOD9604 under the listed names. Private self-affirmed GRAS claims are not FDA drug approval and do not establish injectable safety.
- Study design
- Official inventory coverage under the compound name and aliases
FDA safety page · limited proposed-route evidence
FDA safety communication
US Food and Drug Administration.
FDA cites immunogenicity, peptide-impurity, and API-characterization concerns and notes serious adverse events of unclear causality. Evidence for proposed compounded routes is limited.
- Study design
- Agency safety summary
WADA 2026 · GH fragments
Sports rule
World Anti-Doping Agency, effective 1 January 2026.
Growth-hormone fragments are prohibited under S2 for athletes covered by the Code.
- Study design
- Binding sport rule for covered athletes
Studies and sources
FDA 2024 review · identity, trials, quality
FDA staff briefing document
US Food and Drug Administration, November 2024.
FDA defined free-base AOD9604 as a 16-amino-acid Tyr-hGH177-191 fragment with a Cys7-Cys14 disulfide, separated it from AOD9604 acetate, reviewed obesity and safety data, identified formulation and impurity gaps, and concluded the criteria weighed against 503A bulks-list inclusion.
- Study design
- Regulatory evidence and quality review
ASX 2007 · weight-loss endpoints missed
Sponsor exchange disclosure
Metabolic Pharmaceuticals Ltd, Australian Securities Exchange announcement, 21 February 2007.
The sponsor disclosed that its 24-week randomized obesity trial enrolled 536 people and did not show a significant AOD9604 effect on the primary or secondary weight-loss endpoints. It terminated the obesity program. Subgroup signals were exploratory and did not rescue the overall result.
- Participants / model
- Adults with obesity in a diet-and-exercise program
- Treatment
- Oral AOD9604 at 0.25, 0.5, or 1 mg daily versus placebo
- Follow-up
- 24 weeks after a placebo run-in
- Study design
- Randomized, double-blind, placebo-controlled Phase 2B trial
- Funding
- Metabolic Pharmaceuticals Ltd
Six-trial summary · sponsor-affiliated
Pooled clinical safety report
Stier H, Vos E, Kenley D. Journal of Endocrinology and Metabolism, 2013.
The paper summarizes six trials with 893 participants using single intravenous or oral exposure through 24 weeks. It reports no treatment-related serious event, no anti-AOD9604 antibodies in tested subsets, and no material IGF-1 or glucose signal. The authors included company personnel, the studies were heterogeneous, and subcutaneous use was not tested.
- Participants / model
- 893 participants across six sponsor trials, mainly adults with obesity
- Treatment
- Single IV doses or oral AOD9604 across multiple schedules
- Follow-up
- Single dose through 24 weeks
- Study design
- Sponsor-affiliated pooled safety narrative across six trials
- Funding
- Metabolic Pharmaceuticals program
The individual studies were not all independently peer-reviewed.
Read the original sourceNCT03865953 · primary endpoint negative
Posted randomized trial results
ClinicalTrials.gov NCT03865953.
Fifty-three adults entered a randomized crossover trial of 30 mg oral LAT8881 twice daily. Mean pain changed by -0.87 with LAT8881 and -0.74 with placebo; the net difference was -0.14 points, 95% CI -0.76 to 0.49, P=0.67.
- Participants / model
- Adults with diabetic peripheral neuropathy or post-herpetic neuralgia
- Treatment
- Oral LAT8881 30 mg twice daily versus placebo
- Follow-up
- Four weeks per crossover period
- Study design
- Randomized, double-blind, placebo-controlled crossover trial
- Funding
- Lateral Pharma Pty Ltd
NCT04153409 · no significant pain timepoint
Posted randomized trial results
ClinicalTrials.gov NCT04153409.
Twenty-one adults entered a randomized crossover proof-of-concept trial. None of the seven posted active-versus-placebo pain comparisons from 30 minutes through 24 hours was statistically significant; the smallest P value was 0.1488 at two hours.
- Participants / model
- Adults treating an acute migraine attack
- Treatment
- Single 60 mg oral LAT8881 dose versus placebo
- Follow-up
- Pain measured through 24 hours
- Study design
- Randomized, placebo-controlled crossover proof-of-concept trial
- Funding
- Lateral Pharma Pty Ltd
NCT05298306 · small safety and pain study
Posted randomized trial results
ClinicalTrials.gov NCT05298306.
The two-part study enrolled 26 adults. Part A found no serious or grade 3-4 events after single IV doses. Part B compared 1.8 mg/kg with placebo in a 17-per-period crossover and posted no persuasive separation across the repeated six-hour pain measurements.
- Participants / model
- Adults with lumbar radicular pain
- Treatment
- Single IV LAT8881 doses from 0.8 to 1.8 mg/kg or placebo
- Follow-up
- Safety through 14 days; pain through six hours
- Study design
- Randomized, double-blind, placebo-controlled two-part study
- Funding
- Lateral Pharma Pty Ltd
FDA safety page · limited proposed-route evidence
FDA safety communication
US Food and Drug Administration.
FDA cites immunogenicity, peptide-impurity, and API-characterization concerns and notes serious adverse events of unclear causality. Evidence for proposed compounded routes is limited.
- Study design
- Agency safety summary
FDA GRAS records · no AOD9604 notice
Regulatory database record set
US FDA GRAS Notice Inventory records.
The FDA GRAS Notice Inventory contained no entry or response letter for AOD9604 under the listed names. Private self-affirmed GRAS claims are not FDA drug approval and do not establish injectable safety.
- Study design
- Official inventory coverage under the compound name and aliases
WADA 2026 · GH fragments
Sports rule
World Anti-Doping Agency, effective 1 January 2026.
Growth-hormone fragments are prohibited under S2 for athletes covered by the Code.
- Study design
- Binding sport rule for covered athletes
Why is AOD9604 in D tier?
The D grade reflects human exposure across nearly 900 participants, mainly with oral dosing, and repeated failure to show a persuasive clinical benefit.